Despite decades of research linking depression and alcohol use disorders (AUD), our understanding of their shared etiologies remains understudied, especially the importance of their emergence during adolescence, a period of increased susceptibility for AUD. This application describes a study of affective and neurobiological risk factors for the onset of AUD during adolescence. The aims of the study are to: 1) Identify the main effects and interactions among premorbid affective, neurobiological, genetic, and environmental factors as they relate to the risk to develop AUD;2) Determine which combinations of these factors predict the eventual development of AUD during adolescence;and 3) Examine the consequences of AUD on adolescent brain development. The design is aimed at disentangling how these risk factors are involved in the development of AUD moderated by preexisting risk for depression. This will be accomplished by selecting two samples of adolescents, aged 12 to 14 years at the time of initial assessment, who have either high or low familial loading for depression and following them annually over a three year period into late adolescence. Measures will include: the assessment of mood and negative affect;functional imaging of neural circuitry subserving affective behaviors;genetic polymorphisms involved in serotonin neurotransmission;exposure to acute/chronic stressors;and dimensional assessments of alcohol use as well as disorders. The short-term goals of this work are to understand the etiologic links between depression and AUD and ultimately their emergence during adolescence. The long-term goals are to identify pathways and mechanisms involved in the development of AUD in ways that will inform early intervention and prevention strategies.